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Adjuvant Therapies for Cancer Treatment: 2nd Edition
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Adjuvant Therapies for Cancer Treatment: 2nd Edition

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 54047

Special Issue Editor

Prof. Dr. Fuyi Wang

E-Mail Website
Guest Editor
CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
Interests: anticancer drug design; natural bioactive products; interactomics of drugs; chemical biology of drugs; mass spectrometry; mass spectrometry imaging; chemical proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To improve cancer survival and prevent the recurrence of the disease and metastasis, we need to find new compounds and therapeutic strategies, as well as apply drug repurposing and combined therapies. This means that better adjuvant therapies to improve cancer cures need to be found in the next decade.

Adjuvant therapy may take the form of chemotherapy, radiotherapy, biological therapy, hormone therapy, and targeted therapy.

Adjuvant therapy is used after an initial treatment (such as surgery) or before as a neoadjuvant. Both applications have advantages (such as reducing tumor size, preventing tumor cells from spreading/metastasis, and eliminating any remaining malignant cells after surgery and disease recurrence) and disadvantages (such as serious side effects).

Omics studies and biological approaches have brought about a lot of knowledge of alterations and signaling deregulations in several cancer types and profiles related to outcome and drug efficacy. Cancer resistance occurs in different types of tumors and patients under different treatments, where some therapies are associated with specific resistance mechanisms (such as drug efflux, autophagy, apoptosis blockage, metabolism reprogramming, mutations, and stemness). However, the next steps in oncology will be to connect molecular data with clinical practice and offer a potential and specific protocol to the patient for cancer treatment.

This Special Issue is dedicated to illustrating new findings in adjuvant therapy applied for cancer treatment and highlighting the gaps and new directions in this field.

Prof. Dr. Fuyi Wang
Guest Editor

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Keywords

  • drug repurposing
  • combined therapies
  • new compounds
  • drug resistance
  • chemosensitization
  • antitumoral strategies

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Published Papers (11 papers)

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Research

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16 pages, 1561 KB  
Article
L-Arginine as an Adjuvant Chemosensitizer: Enhancement of Intestinal Permeability and Cytotoxic Activity of Doxorubicin
by Ghada Saad, Rana M. Alquwayi, Hanin B. Alanazi, Farah B. Aldahmashi, Aryam M. Alahmary, Shouq K. Almutairi, Fatima R. Alshammari, Ghadah T. Alshammari, Afnan J. Alrashidi, Norah K. Aldousari, Haifa F. Alsubiei, Lama H. Alanazi, Meaad H. Aldossary and Amal A. Sultan
Pharmaceuticals 2026, 19(4), 546; https://doi.org/10.3390/ph19040546 - 28 Mar 2026
Viewed by 490
Abstract
Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as [...] Read more.
Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as a potential adjuvant that could improve the drug distribution and cytotoxic effectiveness of chemotherapeutics. This study aimed to explore the multifunctional effect of L-arginine on the intestinal absorption and anti-breast cancer activity of doxorubicin. Methods: The rabbit in situ intestinal perfusion technique was employed to investigate the membrane transport parameters of doxorubicin both in the absence and presence of L-arginine. Furthermore, the effect of L-arginine on the cytotoxic activity of doxorubicin against breast cancer cells (MCF-7) was assessed using the MTT assay. Results: Co-perfusion of L-arginine with doxorubicin enhanced the fraction of doxorubicin absorbed, with a recorded 4.3-fold enhancement in the jejuno-ileum and a 1.5-fold enhancement in the colon segment. In MCF-7 cells, co-treatment with L-arginine resulted in a significant potentiation of doxorubicin cytotoxicity. At L-arginine concentrations of 10 μM and 50 μM, the recorded IC50 decreased from 41.3 μM to 8.2 μM and to 22.1 μM, respectively. The superior efficacy of 10 μM L-arginine compared to 50 μM reflected a biphasic concentration-dependent response. Conclusions: L-arginine modulated two critical aspects of doxorubicin efficacy, intestinal absorption and cytotoxic activity. The biphasic response emphasizes the importance of L-arginine dose optimization. These findings support the potential of L-arginine as a safe adjuvant for developing oral doxorubicin formulations. This approach can reduce the dose-related toxicity of doxorubicin and improve therapeutic outcomes. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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13 pages, 1548 KB  
Article
Multitargeting Pt(IV) Anticancer Prodrugs Bearing Mono- and Bis-Probenecid Ligands in Axial Positions: Synthesis and Evaluation of Biological Activity
by Panxing Qiu, Yu Zhang, Yang Dou, Zhijin Cheng, Xiaoqin Wu, Silong Zhang, Fuyi Wang and Kui Wu
Pharmaceuticals 2026, 19(3), 386; https://doi.org/10.3390/ph19030386 - 27 Feb 2026
Viewed by 351
Abstract
Background: To battle the side effects of anticancer Pt(II) drug cisplatin, the development of photoactivatable and/or intracellular reduction-activatable Pt(IV) prodrugs has become a promising strategy. Methods: Herein, two novel Pt(IV) prodrugs, namely, cis,cis,trans-[PtIV(NH3) [...] Read more.
Background: To battle the side effects of anticancer Pt(II) drug cisplatin, the development of photoactivatable and/or intracellular reduction-activatable Pt(IV) prodrugs has become a promising strategy. Methods: Herein, two novel Pt(IV) prodrugs, namely, cis,cis,trans-[PtIV(NH3)2(Cl)2(OH)(probenecid)]) (SPP) and cis,cis,trans-[PtIV(NH3)2(Cl)2(probenecid)2] (DPP) bearing mono- and di-probenecid at the axial positions of oxoplatin have been synthesized via covalently linking of carboxylate group in probenecid, which is a well-established clinic drug by inhibiting organic anion transporter 1 (OAT1) to reduce cisplatin-induced nephrotoxicity, with the axial hydroxyl group(s) in oxoplatin. The promising cytotoxicity of SPP and DPP against MCF-7, T47D breast cancer cells and the MDA-MB-231 triple-negative breast cancer cells was evaluated, and the mechanism of action of the two Pt(IV) prodrugs was investigated by apoptosis assay and Western blot assay. Results: SPP exhibits a comparable cytotoxicity to cisplatin against MCF-7 and T47D breast cancer cells, while it shows 2.1-fold higher cytotoxicity than cisplatin against MDA-MB-231 cells. DPP was shown to be more cytotoxic than SPP, and exhibits 8.7-, 7.5-, and 2.3-fold higher cytotoxicity than cisplatin against MCF-7, T47D, and MDA-MB-231 cells, respectively. Apoptosis assays revealed a similar early-apoptotic cell death mechanism to cisplatin for both SPP and DPP. The enhanced cellular and nuclear uptake of DPP compared to cisplatin contributes to its promising anticancer efficacy. DPP can bind to OAT1 in cancer cells, which may synergistically enhance the cytotoxicity of the Pt(IV) anticancer prodrugs. Conclusions: The direct conjugation of probenecid to the axial positions of oxoplatin confers the resulting Pt(IV) prodrugs a multitargeting property, significantly promoting the cytotoxicity of the resulting Pt(IV) complexes. This finding provides a practical strategy for drug design and cancer treatment based on platinum complexes. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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16 pages, 1766 KB  
Article
Antitumor Activity of the ACC Inhibitor Firsocostat in Breast Cancer Cell Lines: A Proof-of-Concept In Vitro Study
by Simona Picerno, Eugenia Giglio, Martina Giuseffi, Marcello Radino, Marzia Sichetti and Marisabel Mecca
Pharmaceuticals 2026, 19(2), 201; https://doi.org/10.3390/ph19020201 - 24 Jan 2026
Viewed by 650
Abstract
Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric [...] Read more.
Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric inhibitor of acetyl-CoA carboxylase (ACC), has previously been investigated in metabolic diseases but has never been evaluated in breast cancer models. This study aimed to assess the antitumor effects of firsocostat on breast cancer cell lines. Methods: We investigated the cytotoxic and metabolic effects of firsocostat in four breast cancer cell lines—MCF7 (luminal A HR+), SK-BR-3 (HER2-positive), MDA-MB-231 (triple-negative), and HCC1937 (triple-negative, BRCA1-mutated)—together with the non-tumorigenic MCF-10A line. Dose- and time-dependent responses were evaluated using phase-contrast microscopy for morphological evaluation, Trypan Blue exclusion assays, and MTS-based viability assays. Results: Firsocostat significantly reduced cell viability across all breast cancer subtypes in a concentration- and time-dependent manner, with IC50 values ranging from 80 to 93 µM. In contrast, non-tumorigenic MCF-10A cells were less affected, indicating a selective cytotoxic effect toward malignant cells. Conclusions: Firsocostat exerts robust cytotoxic effects in breast cancer models, identifying it as a promising metabolism-targeting therapeutic candidate capable of selectively impairing breast cancer cell survival by disrupting fatty acid biosynthesis. These results indicate that firsocostat could represent a viable candidate as a metabolic-based therapeutic approach for breast cancer. Given its established clinical safety profile in metabolic diseases, firsocostat warrants further preclinical investigation and supports further mechanistic and preclinical evaluation. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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22 pages, 5268 KB  
Article
Herba Patriniae Component Linarin Induces Cell Cycle Arrest and Senescence in Non-Small-Cell Lung Cancer Associated with Cyclin A2 Downregulation
by Wen Xie, Xia Li, Dongmei Huang, Jiana Xu, Minghan Yu, Yanping Li and Qing K. Wang
Pharmaceuticals 2026, 19(1), 111; https://doi.org/10.3390/ph19010111 - 8 Jan 2026
Viewed by 564
Abstract
Background: Non-small-cell lung cancer (NSCLC) remains a major therapeutic challenge due to its high incidence and mortality. Herba Patriniae (HP), a traditional Chinese medicine, has long been used for respiratory disorders and exhibits anti-cancer potential. However, the therapeutic effects of HP on [...] Read more.
Background: Non-small-cell lung cancer (NSCLC) remains a major therapeutic challenge due to its high incidence and mortality. Herba Patriniae (HP), a traditional Chinese medicine, has long been used for respiratory disorders and exhibits anti-cancer potential. However, the therapeutic effects of HP on NSCLC and the underlying mechanisms have not been fully elucidated. Methods: Network pharmacology was applied to identify the core active components of HP and their potential targets in NSCLC. The anti-cancer effects of the core HP component Linarin on the malignant phenotypes of NSCLC cells were characterized using Tumor Protein P53 (p53) wild-type A549 and p53-null H1299 cell lines with Cell Counting Kit-8 (CCK-8), EdU fluorescence staining, colony formation, apoptosis analysis, cell cycle analysis, and senescence-associated β-galactosidase (SA-β-gal) staining, together with molecular docking and Western blotting analyses. Results: Network pharmacology analysis identified Linarin as the core active component of HP and screened out six hub targets, including Cyclin Dependent Kinase 1/4 (CDK1/4), Cyclin A2/B1 (CCNA2/B1), and Checkpoint Kinase 1/2 (CHEK1/2), which were found to be mainly enriched in cell cycle and senescence pathways. In vitro assays showed that Linarin dose-dependently (0–200 μM) inhibited NSCLC cell proliferation, induced G0/G1 phase arrest, and promoted cellular senescence and apoptosis in both cell lines, irrespective of p53 status. Molecular docking confirmed strong binding affinities between Linarin and the hub targets, and Western blotting confirmed that Linarin downregulated CCNA2/B1 and CHEK1. Conclusions: This study demonstrates that Linarin, the core active component of HP, exerts potent anti-NSCLC effects by inducing G0/G1 arrest, senescence, and apoptosis. These effects are associated with the downregulation of key cell cycle regulators, including CCNA2/B1 and CHEK1. Together, these findings highlight the potential of Linarin as a promising therapeutic option for NSCLC. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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18 pages, 3110 KB  
Article
Integrated Molecular Analysis of Thymoquinone–Methotrexate Synergy in Breast Cancer Cells: Apoptosis, Oxidative Stress, and Pathway Modulation
by Senem Alkan Akalın, Yasemin Afşin, İlhan Özdemir, Mehmet Cudi Tuncer and Şamil Öztürk
Pharmaceuticals 2025, 18(10), 1551; https://doi.org/10.3390/ph18101551 - 15 Oct 2025
Cited by 4 | Viewed by 1299
Abstract
Background/Objectives: Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, highlighting the urgent need for effective and less toxic therapeutic strategies. Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, possesses antioxidant and anticancer activities. Methotrexate (MTX), a [...] Read more.
Background/Objectives: Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, highlighting the urgent need for effective and less toxic therapeutic strategies. Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, possesses antioxidant and anticancer activities. Methotrexate (MTX), a widely used folate antagonist, is an established chemotherapeutic agent but is limited by toxicity and resistance. This study aimed to investigate the potential synergistic effects of TQ and MTX in estrogen receptor-positive MCF-7 breast cancer cells. Methods: MCF-7 cells were exposed to TQ (0–100 μM), MTX (0–10 μM), and their combinations for 24–72 h. Cell viability was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and drug interactions were evaluated using the Chou–Talalay method. Apoptosis was quantified by Annexin V/Propidium Iodide (PI) flow cytometry, and cell cycle distribution was analyzed by PI staining. Intracellular reactive oxygen species (ROS) generation was measured using a 2′,7′-Dichlorofluorescin diacetate (DCFH-DA) assay, while antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT)) activities were quantified spectrophotometrically. Gene expression of Bax, Bcl-2, NF-κB, MMP-2, and MMP-9 was determined by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: TQ and MTX each reduced cell viability in a dose- and time-dependent manner, while combination treatment significantly enhanced cytotoxicity compared with single agents (p < 0.01). Combination Index (CI) values < 1 confirmed a synergistic interaction, particularly at 50 μM TQ + 5 μM MTX and 100 μM TQ + 10 μM MTX. Combination therapy increased total apoptosis up to 83.6%, markedly elevated the Bax/Bcl-2 ratio, and enhanced caspase-3 activation. Cell cycle analysis revealed pronounced G2/M arrest. ROS levels increased approximately six-fold, accompanied by significant suppression of SOD and CAT activities. qRT-PCR results demonstrated upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic B-cell lymphoma 2 (Bcl-2), nuclear factor kappa B (NF-κB), matrix metalloproteinase (MMP)-2, and MMP-9. Conclusions: TQ potentiates the anticancer activity of MTX in MCF-7 breast cancer cells by synergistically inducing apoptosis, oxidative stress, and cell cycle arrest while suppressing metastasis-related genes. This combination may represent a promising therapeutic strategy for breast cancer, warranting further validation in in vivo and clinical studies. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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14 pages, 3607 KB  
Article
Association of Erythrocyte-Related Indices with Immune-Related Adverse Events and Survival of Lung Cancer Patients Receiving Immune Checkpoint Inhibitors
by Zhan Wang, Ting Zou, Chen-Wei Liao, Xiang-Ping Li, Zhao-Qian Liu, Ze-Fu Liu and Juan Chen
Pharmaceuticals 2025, 18(9), 1299; https://doi.org/10.3390/ph18091299 - 29 Aug 2025
Viewed by 1140
Abstract
Background: Lung cancer has the highest lethality rate among malignancies worldwide. Immunotherapy is one of the common treatments for lung cancer patients. There are two main types of immunotherapies: one targets programmed cell death 1 (PD-1), and the other targets programmed cell [...] Read more.
Background: Lung cancer has the highest lethality rate among malignancies worldwide. Immunotherapy is one of the common treatments for lung cancer patients. There are two main types of immunotherapies: one targets programmed cell death 1 (PD-1), and the other targets programmed cell death ligand 1 (PD-L1). These two belong to the class of immune checkpoint inhibitors (ICIs). However, immune-related adverse reactions (irAEs) were the main reasons affecting its clinical therapeutic effect. Methods: This retrospective cohort study analyzed red blood cell count (RBC), hematocrit (HCT), erythrocyte mean corpuscular volume (MCV) and immunotherapy outcomes in 920 lung cancer patients receiving immunotherapy from April 2019 to May 2023. Results: We found that high levels of RBC (>4.105 × 109, p = 0.007, OR = 0.467, 95%CI: 0.268~0.812) and MCV (>86.35, p = 0.017, OR = 0.0.441, 95%CI: 0.224~0.865) were significantly related to the better response of ICIs immunotherapy in patients. Patients with high levels of HCT (>39.75%, p = 0.035, OR = 0.737, 95%CI: 0.555~0.979) may have a lower rate of irAEs occurrence. Meanwhile, patients with a low level of RBCs (≤4.635 × 109, p < 0.001, OR = 1.636, 95%CI: 1.365~1.960) may have a longer period of PFS (progression-free survival), and patients with RBC (≤4.43 × 109, p = 0.033, OR = 0.480, 95%CI: 0.244~0.941) may have a longer time of OS (overall survival). Conclusions: The findings indicate that the levels of RBC, MCV and HCT were significantly associated with the response and irAEs of ICIs in lung cancer patients. The levels of RBC might act as a possible biomarker for predicting the survival of lung cancer patients who are receiving ICI therapy. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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16 pages, 1346 KB  
Article
In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
by Mehmet Uğur Karabat, Mehmet Cudi Tuncer and İlhan Özdemir
Pharmaceuticals 2025, 18(6), 854; https://doi.org/10.3390/ph18060854 - 7 Jun 2025
Cited by 1 | Viewed by 1299
Abstract
Background/Objectives: Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in [...] Read more.
Background/Objectives: Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in combination with Cisplatin, on the human epidermoid carcinoma cell line A431. Materials and Methods: A431 cells were cultured under standard conditions and treated with different concentrations of Hesperidin and Cisplatin for 48 h. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-3/7 activity assays. Expression levels of Bax, caspase-3/7, and survivin were measured by RT-qPCR. Results: Hesperidin significantly reduced cell viability at both 24 and 48 h. Annexin V/PI staining revealed increased apoptosis, with the highest apoptotic ratio in the Hesperidin + Cisplatin group (p < 0.001). Caspase-3/7 activity was markedly elevated in Hesperidin-treated cells. RT-qPCR showed upregulation of Bax and caspase-3/7 and downregulation of survivin. Conclusions: Hesperidin demonstrated significant cytotoxic and pro-apoptotic effects in A431 cells. When combined with Cisplatin, a synergistic enhancement of apoptosis was observed. These findings support the potential of Hesperidin as a complementary agent in carcinoma therapy, pending further in vivo and clinical validation. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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23 pages, 2798 KB  
Article
The Cordyceps Genus as a Potential Source of Bioactive Compounds for Adjuvant Cancer Therapy: A Network Pharmacology Approach
by Jose Luis Gonzalez-Llerena, Daniela Treviño-Almaguer, Jesus Alejandro Leal-Mendez, Gael Garcia-Valdez, Arely Guadalupe Balderas-Moreno, Michel Stéphane Heya, Isaias Balderas-Renteria, María del Rayo Camacho-Corona and Bryan Alejandro Espinosa-Rodriguez
Pharmaceuticals 2025, 18(5), 667; https://doi.org/10.3390/ph18050667 - 30 Apr 2025
Cited by 2 | Viewed by 4416
Abstract
Background/Objectives: Cancer remains one of the leading causes of mortality globally, underscoring the need for novel therapeutic strategies capable of targeting multiple molecular pathways simultaneously. Natural products, particularly fungal-derived metabolites from the genus Cordyceps, represent promising candidates due to their diverse biological [...] Read more.
Background/Objectives: Cancer remains one of the leading causes of mortality globally, underscoring the need for novel therapeutic strategies capable of targeting multiple molecular pathways simultaneously. Natural products, particularly fungal-derived metabolites from the genus Cordyceps, represent promising candidates due to their diverse biological activities. Although previous studies have indicated the anticancer potential of Cordyceps species, systematic characterization of their molecular targets has been limited. This study aimed to comprehensively identify and evaluate Cordyceps metabolites as potential multitarget anticancer agents through a network pharmacology approach. Methods: A total of 129 metabolites previously reported in the literature from polar aqueous, alcoholic, and non-polar extracts of Cordyceps were compiled and chemically classified using ChemMine tools. Structure-based target prediction and pathway enrichment analyses were performed to investigate their potential biological targets. Predicted molecular targets were cross-referenced with differentially expressed genes in breast, colorectal, and lung cancers to identify hub proteins. Molecular docking simulations were conducted to assess binding affinities of metabolites to key oncogenic targets, and SwissADME was utilized for pharmacokinetic profiling. Results: The analysis revealed that Cordyceps metabolites targeted critical oncogenic pathways, including cell cycle regulation, DNA replication, and apoptosis. Hub proteins such as TYMS, AURKA, and CDK1 were identified as primary targets. Docking simulations highlighted metabolites such as cordycepsidone A, jiangxienone, and flazin, demonstrating binding affinities comparable or superior to clinically used inhibitors. Pharmacokinetic profiling identified several metabolites with favorable drug-like properties, supporting their potential as lead compounds. Conclusions:Cordyceps extracts contain structurally diverse metabolites capable of modulating multiple cancer-relevant molecular targets, providing a robust foundation for their development into multitarget anticancer therapies. This integrative network pharmacology approach underscores the potential of fungal metabolites in oncology drug discovery. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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22 pages, 5125 KB  
Review
Ivermectin as an Alternative Anticancer Agent: A Review of Its Chemical Properties and Therapeutic Potential
by Kimberly Naula Robalino, Oscar Vivanco-Galván, Juan Carlos Romero-Benavides and Yuliana Jiménez-Gaona
Pharmaceuticals 2025, 18(10), 1459; https://doi.org/10.3390/ph18101459 - 28 Sep 2025
Cited by 3 | Viewed by 34956
Abstract
Background: Ivermectin has recently garnered significant scientific attention for its potential anticancer properties. Objective: This research aims a comprehensive literature review to evaluate IVM’s chemical characteristics and assess its applicability as an alternative therapeutic strategy in oncology. Methods: The methodology involved a systematic [...] Read more.
Background: Ivermectin has recently garnered significant scientific attention for its potential anticancer properties. Objective: This research aims a comprehensive literature review to evaluate IVM’s chemical characteristics and assess its applicability as an alternative therapeutic strategy in oncology. Methods: The methodology involved a systematic search and critical appraisal of data from peer-reviewed scientific databases, focusing on structural analyses, such as nuclear magnetic resonance (NMR), crystallography, and in silico modeling, as well as preclinical experimental studies. Results: The review highlights IVM’s distinct physicochemical profile, including high lipophilicity, poor aqueous solubility, and moderate acid stability, which collectively affect its bioavailability and pharmacokinetic behavior. Mechanistically, IVM has been shown to modulate multiple oncogenic signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, and STAT3. These interactions contribute to the induction of apoptosis, inhibition of tumor cell proliferation, and modulation of the tumor microenvironment across a range of malignancies. Despite encouraging preclinical evidence, clinical validation remains limited. Conclusions: Further investigation is needed to optimize IVM’s formulation for enhanced solubility and targeted delivery, as well as to design robust clinical trials assessing its safety and efficacy in oncology settings. This review provides a foundational framework for future interdisciplinary research on drug repurposing and highlights the potential of IVM as a cost-effective and accessible adjunct or alternative to modern cancer therapy. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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45 pages, 7779 KB  
Review
Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges
by Hussein Sabit, Shaimaa Abdel-Ghany, Yasser Albrahim, Al-Hassan Soliman Wadan, Sanaa Rashwan, Rebekka Arneth and Borros Arneth
Pharmaceuticals 2025, 18(7), 961; https://doi.org/10.3390/ph18070961 - 26 Jun 2025
Cited by 8 | Viewed by 3161
Abstract
Breast cancer (BC) poses a significant clinical challenge due to late metastatic recurrence, driven by dormant disseminated tumor cells (DTCs). This review emphasizes the urgency of addressing tumor dormancy to reduce metastatic relapse, a major contributor to BC mortality. DTCs evade conventional therapies [...] Read more.
Breast cancer (BC) poses a significant clinical challenge due to late metastatic recurrence, driven by dormant disseminated tumor cells (DTCs). This review emphasizes the urgency of addressing tumor dormancy to reduce metastatic relapse, a major contributor to BC mortality. DTCs evade conventional therapies and immune surveillance, reactivating unpredictably, thus necessitating targeted strategies. Current research is fragmented, with conflicting data, inadequate models, and a lack of biomarkers hindering progress. This review synthesizes these gaps and proposes actionable priorities, advocating for integrated, standardized approaches. It highlights the roles of single-cell multi-omics, spatial transcriptomics, and humanized long-term models in unraveling dormancy mechanisms. The review also emphasizes macrophage-targeted therapies, dormancy-specific trials, and biomarker validation, offering paths to clinical translation. Ultimately, this work emphasizes the urgent need for integrated multi-omics approaches, including single-cell and spatial transcriptomics, combined with advanced computational analysis. Moreover, this review critically analyzes the existing research landscape, meticulously identifying key gaps, and proposing concrete, forward-looking directions for both fundamental research and clinical translation in the challenging field of BC dormancy. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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12 pages, 7571 KB  
Case Report
Selumetinib in Adult Neurofibromatosis 1 with Plexiform Neurofibroma
by Carlen A. Yuen, Eleanor Chu, Ryan O’Connell, Bryan K. Sun, Raj Vyas, Michelle Zheng, Emma Elliott and Changrui Xiao
Pharmaceuticals 2025, 18(7), 1039; https://doi.org/10.3390/ph18071039 - 13 Jul 2025
Viewed by 4941
Abstract
Background/Objectives: Neurofibromatosis Type 1 (NF1) plexiform neurofibroma (PN) can cause morbidity, including disfigurement that can negatively impact social functioning. Historically, the mainstay treatment is surgical resection. However, complete resection is often prohibitive due to multiple nerve involvement. Moreover, post-operative recurrence is common. MEK [...] Read more.
Background/Objectives: Neurofibromatosis Type 1 (NF1) plexiform neurofibroma (PN) can cause morbidity, including disfigurement that can negatively impact social functioning. Historically, the mainstay treatment is surgical resection. However, complete resection is often prohibitive due to multiple nerve involvement. Moreover, post-operative recurrence is common. MEK inhibitors, including selumetinib and mirdametinib, have recently changed the treatment paradigm for these tumors. In 2020, selumetinib was FDA-approved for pediatric NF1 patients with inoperable symptomatic PNs, but selumetinib remains under investigation for their adult counterparts. In 2025, mirdametinib was FDA-approved for use in adults with symptomatic incompletely resectable NF1 PNs. Lower partial response rates have been reported with mirdametinib compared to selumetinib, but direct comparative analyses have not been conducted to establish the superiority of one agent over the other. Results: We present a case of a 38-year-old male with a right facial PN successfully treated with selumetinib, resulting in a 16.77% tumor volumetric reduction over 7 months. Selumetinib was well tolerated in our patient, with an asymptomatic Grade 3 CPK elevation that subsequently improved with a dose reduction. Conclusion: Our case adds to the growing body of evidence suggesting that selumetinib is effective and well tolerated in adult patients with NF1-associated PNs. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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